d‐Fructose Modification Enhanced Internalization of Mixed Micelles in Breast Cancer Cells via GLUT5 Transporters

d ‐Fructose modified poly(ε‐caprolactone)‐polyethylene glycol (PCL‐PEG‐Fru) diblock amphiphile is synthesized via Cu(I)‐catalyzed click chemistry, which self‐assembles with D‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS) into PCL‐PEG‐Fru/TPGS mixed micelles (PPF MM). It has been proven that glucose transporter (GLUT)5 is overexpressed in MCF‐7 cells other than L929 cells. In this study, PPF MM exhibit a significantly higher uptake efficiency than fructose‐free PCL‐PEG‐N₃/TPGS mixed micelles in both 2D MCF‐7 cells and 3D tumor spheroids. Also, the presence of free d ‐fructose competitively inhibits the internalization of PPF MM in MCF‐7 cells other than L929 cells. PPF MM show selective tumor accumulation in MCF‐7 breast tumor bearing mice xenografts. Taken together, PPF MM represent a promising nanoscale carrier system to achieve GLUT5‐mediated cell specific delivery in cancer therapy.

     

Corona[5]arenes Accessed by a Macrocycle-to-Macrocycle Transformation Route and a One-Pot Three-Component Reaction

Corona[5]arenes, a novel type of macrocyclic compound that is composed of alternating heteroatoms and para-arylenes, were synthesized efficiently by two distinct methods. In a macrocycle-to-macrocycle transformation approach, S₆-corona[3]arene[3]tetrazine underwent sequential S_NAr reactions with HS-C₆H₄-X-C₆H₄-SH (X=S, CH₂, CMe₂, SO₂, and O) to produce the corresponding corona[3]arene[2]tetrazines. Different corona[3]arene[2]tetrazine compounds were also constructed in a straightforward manner by a one-pot three-component reaction of HS-C₆H₄-X-C₆H₄-SH (X=S, CH₂, CMe₂, SO₂, and O) with diethyl 2,5-dimercaptoterephthalate and 2 equiv of 3,6-dichlorotetrazine under very mild conditions. All corona[5]arenes adopted 1,2,4-alternate conformational structures in the crystalline state yielding similar nearly regular pentagonal cavities. Both the cavity size and the electronic property of the acquired macrocycles were fine-tuned by the nature of the bridging element X.     

Graphs with No Induced Five‐Vertex Path or Antipath

We prove that a graph G contains no induced ‐vertex path and no induced complement of a ‐vertex path if and only if G is obtained from 5‐cycles and split graphs by repeatedly applying the following operations: substitution, split unification, and split unification in the complement, where split unification is a new class‐preserving operation introduced here.     

Nowhere‐Zero 5‐Flows On Cubic Graphs with Oddness 4

Tutte's 5‐flow conjecture from 1954 states that every bridgeless graph has a nowhere‐zero 5‐flow. It suffices to prove the conjecture for cyclically 6‐edge‐connected cubic graphs. We prove that every cyclically 6‐edge‐connected cubic graph with oddness at most 4 has a nowhere‐zero 5‐flow. This implies that every minimum counterexample to the 5‐flow conjecture has oddness at least 6.     

On the Number of 5‐Cycles in a Tournament

We find a formula for the number of directed 5‐cycles in a tournament in terms of its edge scores and use the formula to find upper and lower bounds on the number of 5‐cycles in any n‐tournament. In particular, we show that the maximum number of 5‐cycles is asymptotically equal to , the expected number 5‐cycles in a random tournament (), with equality (up to order of magnitude) for almost all tournaments.     

利用空间位阻和氢溢流协同作用促进5-羟甲基糠醛选择性加氢制备5-甲基糠醛

Selective hydrogenation is a vital class of reaction. Various unsaturated functional groups in organic compounds, such as aromatic rings, alkynyl (C≡C), carbonyl (C＝O), nitro (-NO₂), and alkenyl (C＝C) groups, are typical targets in selective hydrogenation. Therefore, selectivity is a key indicator of the efficiency of a designed hydrogenation reaction. 5-(Hydroxymethyl)furfural (HMF) is an important platform compound in the context of biomass conversion, and recently, the hydrogenation of HMF to produce fuels and other valuable chemicals has received significant attention. Controlling the selectivity of HMF hydrogenation is paramount because of the different reducible functional groups (C＝O, C-OH, and C＝C) in HMF. Moreover, the exploration of new routes for hydrogenating HMF to valuable chemicals is becoming attractive. 5-Methylfurfural (MF) is also an important organic compound; thus, the selective hydrogenation of HMF to MF is an essential synthetic route. However, this reaction has challenging thermodynamic and kinetic aspects, making it difficult to realize. Herein, we propose a strategy to design a highly efficient catalytic system for selective hydrogenation by exploiting the synergy between steric hindrance and hydrogen spillover. The design and preparation of the Pt@PVP/Nb₂O₅ catalyst (PVP = polyvinyl pyrrolidone; Nb₂O₅ = niobium(V) oxide) were also conducted. Surprisingly, HMF could be converted to MF with 92% selectivity at 100% HMF conversion. The reaction pathway was revealed through the combination of control experiments and density functional theory calculations. Although PVP blocked HMF from accessing the surface of Pt, hydrogen (H₂) could be activated on the surface of Pt due to its small molecular size, and the activated H₂ could migrate to the surface of Nb₂O₅ through a phenomenon called H₂ spillover. The Lewis acidic surface of Nb₂O₅ could not adsorb the C＝O group but could adsorb and activate the C-OH group of HMF; therefore, when HMF was adsorbed on Nb₂O₅, the C-OH groups were hydrogenated by the spilled over H₂ to form MF. The high selectivity of this reaction was realized because of the unique combination of steric effects, hydrogen spillover, and tuning of the electronic states of the Pt and Nb₂O₅ surfaces. This new route for producing MF has great potential for practical application owing to its discovered advantages. We believe that this novel strategy can be used to design catalysts for other selective hydrogenation reactions. Furthermore, this study demonstrates a significant breakthrough in selective hydrogenation, which will be of interest to researchers working on the utilization of biomass, organic synthesis, catalysis, and other related fields.      

Spirocyclic azetidines for drug discovery: Novel Boc-protected 7'H-spiro[azetidine-3,5'-furo[3,4-d ]pyrimidines]

A novel spirocyclic scaffold of 7'H-spiro[azetidine-3,5'-furo[3,4-d]pyrimidine] chemotype was synthesized in N-Boc-protected form. However, the scaffold was revealed to be unstable to storage when deprotected. The solution was found in the brief removal of the Boc protecting group and rapid acylation of the liberated NH-azetidine with a carboxylic acid imidazolide.     

Dynamic materials derived from biobased furans: towards the ‘sleeping giant’ awakening

This focus article presents the author’s view on the problems in the development of biorefining strategies based on the use of 5-(hydroxymethyl)furfural (HMF), the key product derived from renewable plant biomass that was recognized as the ‘sleeping giant’ of the sustainable chemistry. The several key problems that hinder the large-scale production of HMF and its applicability in the laboratory organic synthesis and industry are discussed. This minireview is also focused on the development of the dynamic cross-linked polymers with controlled three-dimensional structure based on Diels–Alder reaction of biobased HMF-derived furans with maleimides. Realization of scalable technologies for an efficient production of such ‘smart’ analogues of the traditional petrochemical-based materials could be the basis for the realization of the competitive HMF-promoted biorefining.     

A simple synthesis of natural spinazarins and their analogues

A short simple synthesis of spinazarins (2,3-dihydroxy-naphthazarins or 2,3,5,8-tetrahydroxy-1,4-naphtho-quinones) from available 2,3-dichloronaphthazarin derivatives involves replacement of chlorine atoms with azido groups followed by their acidic hydrolysis. The procedure can be used for the preparative synthesis of natural biologically active spinazarins and their analogues.     

Synthesis and cytotoxicity studies of new 1,2,4-thiadiazole derivatives and their zinc complexes

A new polyfunctional ligand of the thiadiazole family was synthesized. Cytotoxic properties with respect to leukemic cell lines, radiation stability, predicted permeability through the blood–brain barrier and cardiotoxicity of the new ligand and its precursor were determined. New zinc complexes with N-{2-[5-(3-chloro-4-methylphenylamino)-1,2,4-thiadiazol-3-yl]-1-methylethyl}-N-(2,2,6,6-tetramethylpiperidin-4-yl)-amine as the ligand have been obtained.